Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/28/2008
Publication Date: 2/2/2009
Citation: Sunehag, A.L., Man, C.D., Toffolo, G., Haymond, M.W., Bier, D.M., Cobelli, C. 2009. beta-Cell function and insulin sensitivity in adolescents from an OGTT. Obesity. 17(2):233-239. Interpretive Summary: The common occurrence of obesity and obesity-related illnesses, for example reduced sensitivity to insulin and type 2 diabetes, in adolescence is a serious public health concern. Therefore, it is very important to find methods to measure what happens with sensitivity to insulin and formation of insulin during a meal or intake of a sugar drink. In this study, we accomplished this by using sugar labeled with three different heavy (non-radioactive) isotopes. Two were given by vein and one as a drink. Blood samples were drawn at specific time points over a 7-hour period. Eleven normal and overweight adolescents were studied. We found that sensitivity to insulin and formation of insulin could be correctly measured using a glucose drink. In addition, the blood sampling period could be reduced to 3 hours. Thus, our method is a useful tool to measure sensitivity to insulin and formation of insulin in both normal and overweight adolescents.
Technical Abstract: Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7-h, 21-sample OGTT was performed in 11 adolescents. The C-peptide minimal model was identified on C-peptide and glucose data to quantify indices of beta-cell function: static phi(s) and dynamic phi(d) responsivity to glucose from which total responsivity phi was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S(I), which was compared to a reference measure, S(I)(ref), provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of beta-cell function were phi(s) = 51.35 +/- 8.89 x 10(-9)min(-1), phi(d) = 1,392 +/- 258 x 10(-9), and phi = 82.09 +/- 17.70 x 10(-9)min(-1). Insulin sensitivity was S(I) = 14.19 +/- 2.73 x 10(-4), not significantly different from S(I)(ref) = 14.96 +/- 3.04 x 10(-4) dl/kg.min per microU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S(I) can be accurately measured from an oral test. Disposition indices were DI(s) = 1,040 +/- 201 x 10(-14) dl/kg/min(2) per pmol/l, DI(d) = 33,178 +/- 10,720 x 10(-14) dl/kg/min per pmol/l, DI = 1,844 +/- 522 x 10(-14) dl/kg/min(2) per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3-h, 9-sample protocol. OGTT interpreted with C-peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.